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Background: The confirmatory test for sphincter of Oddi dysfunction (SOD) is manometry (SOM) which may be hazardous. When SOM is equivocal, the decision to treat by sphincterotomy, entailing further risk, [...]

Background: Children with abdominal pain, vomiting, and/or bloating often have gastric dysfunction such as delayed gastric emptying (GE). GE studies on children are difficult to perform due to the necessity [...]

Background and Aims: Enteral feed given as a bolus has a half emptying time (t 1/2) of 90 min. No data are available on gastric emptying patterns during continuous nasogastric [...]

Introduction: Identification of LOS by visual inspection at endoscopy is unreliable and often impossible. Knowledge of the sphincter position detected by station pull through manometry (SPM) can not be effectively [...]

Introduction: Sphincter of Oddi dysfunction (SOD) represents a difficult diagnostic challenge. Sphincter of Oddi manometry is the gold standard diagnostic method, but this is technically difficult, carries significant risk, and [...]

Introduction: Patients with globus sensation are usually referred to an ENT specialist for possible malignancy. However, in most patients, flexible laryngoscopy shows no abnormalities, and further management is often unclear. [...]

Compares the symptomatic and physiological response to the treatment of gastro-esophageal reflux disease (GORD) by proton pump inhibitors and by laparoscopic antireflux surgery. Relationship between symptom severity and objective evidence of GORD after medical and surgical treatment; Relationship between the patient's subjectiveand objective response to treatment of GORD.

Little is known about the effect of achalasia and gastroesophageal reflux disease (GERD) on compliance of the esophageal body and the lower esophageal sphincter (LES). Twenty-two patients with achalasia, 14 with GERD, and 14 asymptomatic volunteers were assessed. Recording apparatus consisted of a specially developed PVC bag tied to a compliance catheter, a barostat, and a polygraph. Intrabag pressures were increased incrementally while the bag volume was recorded. In each subject, pressure-volume graphs were constructed for both the esophageal body and LES and the compliance calculated. In achalasia, compliance of the esophageal body was significantly higher (P < 0.01) than in controls, whereas LES compliance was similar. Patients with GERD had a highly compliant LES in comparison to both controls and to patients with achalasia (P < 0.01 and P < 0.001, respectively); however there was no difference in their esophageal body compliance. In conclusion, foregut motility disorders can cause changes in organ compliance that are detectable using a barostat and a suitably designed compliance bag. Further measurement of compliance may provide clues to the pathogenesis of these disorders. [ABSTRACT FROM AUTHOR]

Gastric emptying may be delayed in HIV infection. We aimed to characterize the pattern of gastric emptying in HIV seropositive subjects and correlate the findings with symptoms, as well as to identify possible etiological factors. Solid gastric emptying was measured using scintigraphy in 54 HIV seropositive subjects and 12 HIV seronegative controls. Gastrointestinal symptoms were evaluated using a standardized numerical score, and autonomic function was assessed using spectral analysis of heart rate variability. Fasting and postprandial duodenojejunal activity was recorded using strain gauge manometry catheters. Gastric emptying rate, but not lag phase, was significantly delayed in HIV-infected subjects, particularly those with enteric infections and more advanced disease. Delayed gastric emptying did not correlate with symptoms, autonomic dysfunction, or small intestinal motility. In conclusion, abnormalities found in autonomic function and gastric emptying in HIV infection are multifactorial in nature. The contribution of upper gastrointestinal motor dysfunction to gastric symptoms in such individuals is unclear. [ABSTRACT FROM AUTHOR]

30 to 65% of long distance runners experience gastrointestinal (GI) symptoms related to exercise. Several hypotheses have been postulated; however, the aetiology and pathophysiology are far from clear. The mechanical effect of running on the viscera must be involved in the development of GI symptoms in this sport. Reduction of splanchnic blood flow due to visceral vasoconstriction is another widely supported theory; nevertheless, it does not explain many of the clinical findings. Examination of the GI tract during exercise is a difficult task, and measurements of both orocaecal and whole-gut transit time have shown equivocal results. GI hormones, and especially prostaglandins, may be of crucial importance for the production of symptoms. Intestinal absorption, secretion and permeability may also be altered during exercise, provoking intestinal dysfunction. Factors such as stress, diet, dehydration, infections and other factors need to be analysed in order to present a global view of the hypotheses regarding the aetiology of this common and often overlooked problem. [ABSTRACT FROM AUTHOR]

Introduction Persistent reflux symptoms occur in a subgroup of patients following antireflux surgery. These symptoms can be due failure of the antireflux barrier. GI physiology studies are performed to evaluate the OGJ function and anatomy in these patients. Recent studies with high resolution manometry (HRM) have shown the presence of a dual high pressure zone (HPZ) at the OGJ as an expression of persistent hiatus hernia. However, the relation between dual high pressure zone, oesophageal hypomotility and persistent symptoms is unclear. The aim of this study was to evaluate reflux parameters and oesophageal motility patterns with HRM in a group of symptomatic patients after fundoplication. Methods Ten patients (5 male, 5 female; mean age 55 years) were selected based on the presence of persistent typical reflux symptoms post-Nissen fundoplication. The patients underwent HRM and impedance-pH monitoring ‘off’ PPI. The existence of dual HPZ, oesophageal hypomotility and amplitude of the after-contraction post multiple rapid swallowing (MRS) were evaluated together with acid and non-acid reflux parameters. Increased number of reflux events (post Nissen) was considered if >30/24 h. Results Six out of ten patients had a dual HPZ on HRM. Acid exposure time and number of acid reflux events in these patients was significantly higher than those with a single HPZ (12.7% vs 0.5%, p=0.01). The patients with a dual HPZ more commonly exhibited oesophageal hypomotility and poor response to MRS compared to the patients with a single HPZ (4/6 vs 1/4). In addition more of the patients with a dual HPZ showed impaired acid reflux clearance compared to patients with single HPZ (5/5 vs 1/3). Conclusion HRM and impedance-pH measurement allows a precise assessment of patients with symptoms postfundoplication. Our study suggests that the presence of a dual HPZ on oesophageal HRM is associated with impairment of oesophageal motility and impaired oesophageal acid clearance, and hence may be important in the persistence of GORD symptoms postoperatively. [ABSTRACT FROM PUBLISHER]

Introduction Many patients attending GI physiology units for assessment of dysphagia and GORD also complain of postprandial bloating and/or belching. Excessive fasting aerophagia has been recently described in patients with severe continuous bloating and belching. Exaggerated air swallowing might be more relevant for postprandial symptoms but, thus far, objective assessment of prandial aerophagia and normal values are lacking. Oesophageal impedance can detect air swallowing. We aimed to quantify aerophagia during meals in asymptomatic subjects and patients with postprandial bloating and belching. Methods We assessed aerophagia during meals using ambulatory impedance-pH monitoring in 39 healthy, asymptomatic controls (from the US-Belgian MII-pH Normal value study, Shay . 2004; mean age in original study 39, range 22–62) to establish normal 95% confidence intervals. We identified 38 patients (mean age 43, range 17–74) with postprandial bloating and/or belching who attended the GI physiology unit for assessment of dysphagia or GORD as primary symptoms. Mealtime air swallows were visually identified when swallows were associated with antegrade flow and fast impedance increase (at least 3000 Ω from baseline) in the most distal recording segment. A score of air swallows/10 min mealtime was calculated for each subject. In patients with mealtime exaggerated air swallowing (above 95th percentile of normal values) we examined for evidence of concomitant fasting aerophagia. Results The 95% percentile range of mealtime aerophagia in normal subjects was 6.8 to 9.4 episodes/10 min, mean 8.1. Patients had significantly higher mealtime air swallowing rates than controls (mean 11.8 episodes/10 min, SEM 1.0, p = ). There was no significant difference between predominant bloating and belching subgroups. Only 4 of 23 patients with exaggerated mealtime air swallowing had concomitant fasting aerophagia. OC-054 Prandial aerophagia in normal controls and patients with belching and bloating Conclusion We established normal values of mealtime air swallowing using oesophageal impedance. Patients with postprandial bloating and/or belching exhibit increased aerophagia during meals. Most of these patients do not have fasting aerophagia. Exaggerated air swallowing during meals can now be objectively detected and biofeedback techniques can be attempted to modify such behaviour as a potential therapeutic strategy for these patients with functional GI symptoms. [ABSTRACT FROM PUBLISHER]

Background: Small bowel manometry (SBM) has widely been used to investigate adult patients with gastrointestinal motility disorder. However, the use of this technique to paediatrics is uncommon. The aim of this study was to evaluate feasibility of SBM on paediatric patients with suspected small intestinal motility disorder. Methods: We have performed SBM on 14 paediatric patients (age range 2-10 years) who had symptom(s) including recurrent abdominal pain (n = 10), nausea (n = 5), vomiting (n = 7), abdominal distension (n = 2) and constipation (n = 2). A 3-channel manometry catheter was introduced nasally and placed in the proximal small bowel under fluoroscopic control. Ambulatory recordings were made for 24 hours using a portable recorder. Recorded data were analysed using dedicated software. Results: Four had normal motility when applied to the normal ranges in adults. At least one of the following abnormalities was found in eight patients; possible neuropathy findings including excess of motor activity (n = 3), prolonged Phase III (n = 2), Phase III-like prolonged bursts (n = 3), non-propagated Phase III (n = 2), retrograde propagation of Phase III (n = 2), and Iow-amplitude Phase III (n = 1) suggesting possible myopathy. Intubation failed in two patients due to no migrations of the catheter into the small intestine. Summary: In this study a high proportion of the patients had abnormal small intestinal motility and this suggests that SBM can be used to evaluate those conditions. Normal values during infant and childhood development need establishing before adopting the technique for clinical diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Circadian rhythms for protein transcription have recently been identified in the gut? Environmental synchronizers may reset biological clocks, leading to alteration in gut functions, but alteration in bowel transit due to time zone shifts experienced in long haul flight is yet to be reported. Methods: Six men (Age 33.2 +/- 10.6 years) and 3 women (36.7 +/- 7.2) (mean +/- 1 SD) flew from London to California, USA, and back. As a pre-condition to joining the study, they were on no drugs for digestive diseases. We elicited responses pre-, in-, and post-flight and during foreign stay about their bowel habit, stool form scale and abdominal symptoms using validated questionnaires. Paired t-tests were used to examine significant changes in sleep and stool form scale from the pre-flight level. Stool form scale may be used as o guide to intestinal transit time. Results: Sleep duration and times pre-flight, during foreign stay and post flight were not significantly different (p > 0.05). Additionally, there was no reason to believe that the stool changes were attributable to a drastic change in diet. Abdominal symptoms were unremarkable and did not change during foreign stay or on return home from abroad. All our subjects were normal and had an uneventful stay abroad. Average stool consistency changed significantly (p < 0.01) from a lumpy to smooth consistency to a smooth to soft consistency during foreign stay and persisted 4-5 days into post-flight. The respective stool form sca[es were pre-flight 2.8 +/- 1.0, foreign stay 3.5 +/-1.1, post-flight 3.7 +/-1.2. Summary and Conclusion: During a time zone shift of +/- 8h, while the sleep clock was synchronized with the external chock, gut transit, as measured by the stool form scale, failed to synchronize with the external clock, leading to altered bowel habit. Biologic clocks that regulate gut functions may not adapt as readily to time shifts, as does the sleep clock. [ABSTRACT FROM AUTHOR]

Sphincter of Oddi dysfunction (SOD) is a cause of postcholecystectomy pain. Current gold-standard diagnosis is by measurement of basal pressure by sphincter of Oddi manometry (SOM), and if elevated an endoscopic sphincterotomy (ES) is performed. Both these procedures carry significant complication rates. Hepatobiliary scintigraphy has been promoted as a means of assisting management. Aim: to evaluate hepatobiliary scintigraphy (HBS) as a means of screening for SOD and predicting treatment response. Methods: 21 post-cholecystectomy patients were screened by HBS prior to standard evaluation with SOM during ERCP. HBS was performed using a standard protocol. A semi-quantitative scoring system classified scans as positive (SOD) or negative (no SOD). Two observers reviewed all 21 scintigrams. SOM was regarded as diagnostic of SOD if sphincter base pressure was > 40 mm Hg. If elevated, an ES was performed and a successful result was defined as an improvement in symptoms. Results: 17 of our patients were female, average age 42.4 + 4.0 years. Agreement was 100% between observers. Conclusions: HBS can be interpreted reliably between observers. HBS is a poor screening tool in isolation, but may prove a useful adjunct to manometry in predicting ES outcome. [ABSTRACT FROM AUTHOR]

23 Children aged between 11 months and 15.5 years were seen in our clinic within the period October 01 2001-2002. They presented with feeding difficulties that required oesophageal manometry, among other diagnostic investigations. The commonest symptoms were dysphagia for solids, regurgitation, and vomiting, in order of frequency. Lower Oesophageal Sphincter (LOS) pressure and body motility were measured using a standard eight channel, water perfused adult catheter (3.9 mm diameter) or a 2.3 mm catheter purpose designed for paediatric use (Mediplast). LOS pressure and oesophageal body motility were measured using a Flexilog 4000 recording system. Nine out of 23 patients had a hypertensive LOS (pressure > 26 mm Hg). These patients with hypertensive LOS but without achalasia often had regurgitation and vomiting as major presenting symptoms. Only 2 out of 23 patients had achalasia and only one of the two had a hypertensive LOS. Non-specific motility disorder (7/23), in which there were few peristaltic waves with a majority of simultaneous contractions, was the commonest cause of dysphagia. Of significance was a subgroup (4/23) with a partially relaxing LOS (residual pressure 6-11 mm Hg) but who did not have achalasia. This group had varied symptoms such as vomiting, regurgitation, and dysphagia for solids. A large hiatus hernia (7 cm) was the only finding in an adolescent girl with unexplained vomiting, normal oesophageal body motility, and "normal" OGD. in summary, children with feeding problems who present with regurgitation, vomiting, and dysphagia for solids are most likely to have a hypertensive LOS or non-specific oesophageal dysmotility rather than achalasia. Unexplained vomiting with normal LOS function and body motility may be due to hiatus hernia, which could be missed during OGD. In conclusion, oesophageal manometry is an essential diagnostic tool in the investigation of upper gastrointestinal manifestations. From our experience, it is best suited to... [ABSTRACT FROM AUTHOR]

Flavin adenine dinucleotide (FAD) is an essential cofactor for numerous flavoenzymes present in all living organisms. The biosynthesis of FAD from riboflavin involves two sequential reactions catalyzed by riboflavin kinase and flavin adenine dinucleotide synthase (FADS). Entamoeba histolytica , the protozoan parasite responsible for amebiasis, apparently lacks a gene encoding FADS that share similarity with bacterial and eukaryotic canonical FADS, yet it can synthesize FAD. In this study, we have identified the gene responsible for FADS and thoroughly characterized physiological and biochemical properties of FADS from E. histolytica . Phylogenetic analysis revealed that the gene was likely laterally transferred from archaea. The kinetic properties of recombinant EhFADS were consistent with the notion that EhFADS is of archaeal origin, exhibiting K M and k cat values similar to those of the arachaeal enzyme while significantly differing from the human counterpart. Repression of gene expression of EhFADS by epigenetic gene silencing caused substantial reduction in FAD levels and parasite growth, underscoring the importance of EhFADS for the parasite. Furthermore, we demonstrated that EhFADS gene silencing reduced thioredoxin reductase activity, which requires FAD as a cofactor and makes the ameba more susceptible to metronidazole. In summary, this study unveils unique evolutionary and biochemical features of EhFADS and underscores its significance as a promising drug target in combating human amebiasis.IMPORTANCEFAD is important for all forms of life, yet its role and metabolism are still poorly studied in E. histolytica , the protozoan parasite causing human amebiasis. Our study uncovers the evolutionary unique key enzyme, archaeal-type FADS for FAD biosynthesis from E. histolytica for the first time. Additionally, we showed the essentiality of this enzyme for parasite survival, highlighting its potential as target for drug development against E. histolytica infections.

Gastroesophageal reflux disease (GERD) is commonly encountered in clinical practice in Sri Lanka. However, its prevalence in Sri Lanka is unknown. Our objective was to study the island-wide prevalence of GERD symptoms in Sri Lanka and its associated factors. A total of 1200 individuals aged 18-70 years (male: female 1: 1.16, mean age 42.7 years [SD 14.4 years]). were recruited from all 25 districts of the country, using stratified random sampling. An interviewer-administered, country-validated questionnaire was used to assess the GERD symptom prevalence and associated factors. Weight, height, waist, and hip circumference were measured. Heartburn and/or regurgitation at least once a week, an internationally used criterion for probable GERD was used to diagnose GERD. In this study, GERD symptom prevalence was 25.3% (male 42.1% and female 57.9%). Factors independently associated with GERD were inadequate sleep, snacking at midnight, sleeping within two hours of consuming a meal, skipping breakfast, increased mental stress, and certain medications used such as statins, and antihypertensive medications (p<0.001, univariate and logistic regression analysis). 38.4% of the study population have been using medication for heartburn and regurgitation in the past 3 months and 19.8% were on proton pump inhibitors. To conclude, the prevalence of GERD symptoms in Sri Lanka (25.3%) is higher than its estimated global prevalence of 13.8%. Several meal-related lifestyle habits, mental stress, and the use of some medications are significantly associated with GERD, indicating the importance of lifestyle modification and stress reduction in its management., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wickramasinghe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Supragastric belching (SGB) and aerophagia are behavioral disorders characterized by air induced esophageal distension. SGB is known to be associated with Gastro Esophageal Reflux Disease (GERD). Low Mean Nocturnal Baseline Impedance (MNBI) values support GERD diagnosis. We aimed to assess if chronic esophageal distension by air affects the esophageal mucosa integrity by assessing changes in MNBI., Methods: In a single-center database study, we searched retrospectively for patients with a diagnosis of pathological SGB (n = 146) or aerophagia (n = 34) based on impedance-pH reflux monitoring. During the examined period, patients with a conclusive negative diagnosis of SGB and no evidence of aerophagia were used as a control cohort (n = 191). MNBI at 3, 5, and 17 cm over Lower Esophageal Sphincter (LES) was evaluated. GERD was diagnosed if acid exposure time (AET) >6%. All impedance studies of included patients were prospectively reevaluated., Results: GERD was diagnosed in 31.7% patients with SGB, a rate not different in comparison to patients without SGB (30.8%, p = 0.906). MNBI at 3 and 5 cm above the LES was significantly decreased among patients with SGB. SGB was not correlated with MNBI at 3 cm over the LES, (p: 0.086 OR: 1.000 95% CI: 0.999-1.001) when using multivariate analysis. Moreover no difference was spotted as far as MNBI at 3, 5, and 17 cm over the LES is concerned among patients with or without aerophagia., Conclusion: Even if patients with SGB do show lower MNBI values, esophageal distention due to excessive air movement does not directly lead to impairment of esophageal mucosa integrity., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

DNA polymerases synthesize DNA from deoxyribonucleotides in a semiconservative manner and serve as the core of DNA replication and repair machinery. In eukaryotic cells, there are 2 genome-containing organelles, mitochondria, and plastids, which were derived from an alphaproteobacterium and a cyanobacterium, respectively. Except for rare cases of genome-lacking mitochondria and plastids, both organelles must be served by nucleus-encoded DNA polymerases that localize and work in them to maintain their genomes. The evolution of organellar DNA polymerases has yet to be fully understood because of 2 unsettled issues. First, the diversity of organellar DNA polymerases has not been elucidated in the full spectrum of eukaryotes. Second, it is unclear when the DNA polymerases that were used originally in the endosymbiotic bacteria giving rise to mitochondria and plastids were discarded, as the organellar DNA polymerases known to date show no phylogenetic affinity to those of the extant alphaproteobacteria or cyanobacteria. In this study, we identified from diverse eukaryotes 134 family A DNA polymerase sequences, which were classified into 10 novel types, and explored their evolutionary origins. The subcellular localizations of selected DNA polymerases were further examined experimentally. The results presented here suggest that the diversity of organellar DNA polymerases has been shaped by multiple transfers of the PolI gene from phylogenetically broad bacteria, and their occurrence in eukaryotes was additionally impacted by secondary plastid endosymbioses. Finally, we propose that the last eukaryotic common ancestor may have possessed 2 mitochondrial DNA polymerases, POP, and a candidate of the direct descendant of the proto-mitochondrial DNA polymerase I, rdxPolA, identified in this study., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: Mechanisms underlying perception of dysphagia and chest pain have not been completely elucidated, although oesophageal mucosal afferent nerves might play an important role., Aims: To evaluate the relationship between oesophageal mucosal afferent nerves and the severity of dysphagia and chest pain in oesophageal motility disorders., Methods: We prospectively recruited patients with oesophageal motility disorders having dysphagia and/or chest pain from whom oesophageal biopsies were obtained. High-resolution manometry classified patients into disorders of oesophagogastric junction (OGJ) outflow and disorders of peristalsis. Symptom severity was assessed using validated questionnaires including Brief Oesophageal Dysphagia Questionnaire (BEDQ). Immunohistochemistry was performed on oesophageal biopsies to evaluate the location of calcitonin gene-related peptide (CGRP)-immunoreactive mucosal afferent nerves. Findings were compared to existing data from 10 asymptomatic healthy volunteers., Results: Of 79 patients, 61 patients had disorders of OGJ outflow and 18 had disorders of peristalsis. CGRP-immunoreactive mucosal nerves were more superficially located in the mucosa of patients with oesophageal motility disorders compared to healthy volunteers. Within disorders of OGJ outflow, the location of CGRP-immunoreactive nerves negatively correlated with BEDQ score both in the proximal (ρ = -0.567, p < 0.001) and distal oesophagus (ρ = -0.396, p = 0.003). In the proximal oesophagus, strong chest pain was associated with more superficially located mucosal nerves than weak chest pain (p = 0.04). Multivariate analysis showed superficial nerves in the proximal oesophagus was independently associated with severe dysphagia in disorders of OGJ outflow (p = 0.008)., Conclusions: Superficial location of mucosal nerves in the proximal oesophagus might contribute to symptoms, especially severe dysphagia, in disorders of OGJ outflow., (© 2023 John Wiley & Sons Ltd.)

Most species belonging to the diplomonad genera, Trepomonas and Hexamita , are considered to have secondarily adapted to free-living lifestyles from the parasitic ancestor. Here, we report the annotated transcriptome data of Trepomonas sp. NIES-1444 and Hexamita sp. NIES-1440, the analysis of which will provide insights into the lifestyle transitions., Competing Interests: The authors declare no conflict of interest.

Background: Reflux hypersensitivity (RH) is characterized by normal esophageal exposure to acid and positive correlation of symptoms to reflux episodes. Positivity of Symptomatic Index (SI) and/or Symptom Association Probability (SAP) is used diagnostically, though experts support that concordance of both is needed. We evaluated differences among patients with RH and concordance of SI/SAP or not., Methods: Patients with typical reflux symptoms without previous GERD diagnosis, submitted simultaneously to Ph-Impedance off PPI and high resolution manometry were included. Self-response to PPI was evaluated. Patients showing SI and/or SAP positivity were considered having RH and further classified to definite RH if both SI/SAP were positive or indefinite if only one positive., Key Results: Totally 2659 patients (M/F: 35.6%/64.7%, mean age: 45 ± 14) were included. Final diagnosis was; FH: 21.8%, RH: 29.3% (definite: 14.3%/indefinite: 15%), GERD: 36% and inconclusive GERD: 12.9%. Patients with definite RH showed increased total reflux time, total number of reflux episodes and length of hiatus hernia, and also numerically but not statistically significant increased rates of PPI responsiveness versus indefinite RH and decreased mean nocturnal baseline impedance. Moreover, they showed significantly increased rate of PPI response versus patients with functional heartburn (FH)., Conclusion & Inferences: Some PPI responsiveness is frequent among patients with RH as also with FH, and cannot discriminate those entities clinically when diagnosing RH using SI and/or SAP positive criterion. Patients with RH and SI/SAP concordance differ from patients without. Implementation of a strict RH definition (both SI and SAP positive) can better distinguish RH from FH and should be used in the future., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background/aims: Stress is a known associated factor for gastroesophageal reflux disease (GERD). However, the dynamics between stress and GERD are not fully studied, especially in Sri Lanka. Our objective was to assess it., Methods: For this cross-sectional descriptive study, 1200 individuals (age ranged 18-70 years, mean 42.7 years [SD 14.4 years], 46.1% males), were recruited using stratified random cluster sampling from all 25 districts of Sri Lanka. An interviewer-administered questionnaire, which included a country-validated GERD symptom screening tool, and the Perceived Stress Scale (PSS), was used to assess GERD symptoms and stress. Probable GERD was defined as those having heartburn and/ or regurgitation at least once per week which is on par with globally accepted criteria. Those who did not fulfill these criteria were considered as controls., Results: PSS score was higher in those with probable GERD (mean 13.75 [standard deviation (SD) 6.87]) than in controls (mean 10.93 [SD 6.80]), (p <0.001, Mann-Whitney U test). The adjusted odds ratio for GERD symptoms was 1.96 times higher (95% confidence interval 1.50-2.55) in the moderate to high-stress level compared to the low-stress level participants. PSS score correlated significantly with the GERD screening tool score (R 0.242, p <0.001). Heartburn, regurgitation, chest pain, cough, and burping were significantly frequent in those with moderate to high-stress levels (p <0.001). Those with higher stress scores were more likely to use acid-lowering drugs (p = 0.006)., Conclusions: Individuals exposed to higher levels of stress are more likely to have GERD symptoms. Therefore, stress reduction should be an important part of GERD symptom management., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wickramasinghe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The esophagogastric junction (EGJ) is classified into 3 anatomical subtypes according to lower esophageal sphincter-crural diaphragm (LES-CD) separation. We aimed to assess their relationship to esophageal motility, reflux characteristics, and symptom perception., Methods: We analyzed data from 1740 consecutive patients with typical reflux symptoms, who underwent high resolution manometry and a 24-h pH-impedance study during a 13-year period. A diagnosis of gastroesophageal reflux disease (GERD) was made if acid exposure time (AET) was >6%. EGJ types were classified as 1, 2, or 3, if LES-CD separation was up to 1 cm, 1-3 cm, or ≥3 cm, respectively., Results: EGJ type distribution was 72.2%, 22.1% and 5.7%, for types 1, 2 and 3, respectively. GERD was diagnosed in 31.2% and was more common among patients with EGJ type 2/3 vs. 1 (P<0.001). Length of LES-CD separation significantly correlated with AET and number of reflux episodes. Patients with type 2 or 3 EGJ more often showed ineffective or absent peristalsis compared with type 1 (P=0.008 and P<0.001 respectively). In the multivariate analysis, EGJ type 2/3 correlated with AET (P=0.001) and reflux episodes (P=0.041) but not with positive symptomatic markers or with ineffective/absent peristalsis., Conclusions: Our study confirms that EGJ anatomical morphology is a strong risk factor for GERD and correlates with both AET and the number of reflux events, though the length of separation is more important than the type. The multivariate analysis revealed that EGJ type 2 or 3 was not correlated with symptom perception or esophageal hypomotility., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Aim: Low mean nocturnal baseline impedance (MNBI) values support gastroesophageal reflux disease (GERD) diagnosis. Recent data denote that age and obesity may affect MNBI. We aimed to evaluate diagnostic MNBI cutoffs as also the effect of aging and body mass index (BMI) on MNBI., Methods: In total 311 patients (M/F: 139/172, mean age: 47 ± 13) referred for typical GERD symptoms that have undertaken both high-resolution manometry (HRM) and pH-Impedance studies off PPI were evaluated. MNBI at 3, 5, and 17 cm over lower esophageal sphincter (LES) were evaluated. GERD was diagnosed if acid exposure time (AET) >6%., Results: Mean BMI was 26.6 ± 5.9 kg/cm 2 . GERD was diagnosed in 39.2% and 13.5% had inconclusive GERD. MNBI was correlated to patients' age, BMI, AET, and the length of LES-CD separation and at 3 cm also to the total number of reflux and LES hypotension. In the multivariate analysis MNBI at 3 and 5 cm was independently correlated only to age, BMI, and AET. Patients with definite GERD showed lower MNBI at 3 cm compared with inconclusive GERD though both showed lower values when compared with GERD absence. At 3 cm MNBI ability for diagnosing GERD was good (0.815, p < 0.001 95% CI: 0.766-0.863) with an optimal cutoff point of 1281 Ohm., Conclusion: According to our study findings age and BMI affect independently lower esophageal MNBI values in patients evaluated for GERD. MNBI significantly aids toward GERD diagnosis though in a real-life setting MNBI values much lower than the one previously proposed should be used., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Common buckwheat, Fagopyrum esculentum, is an orphan crop domesticated in southwest China that exhibits heterostylous self-incompatibility. Here we present chromosome-scale assemblies of a self-compatible F. esculentum accession and a self-compatible wild relative, Fagopyrum homotropicum, together with the resequencing of 104 wild and cultivated F. esculentum accessions. Using these genomic data, we report the roles of transposable elements and whole-genome duplications in the evolution of Fagopyrum. In addition, we show that (1) the breakdown of heterostyly occurs through the disruption of a hemizygous gene jointly regulating the style length and female compatibility and (2) southeast Tibet was involved in common buckwheat domestication. Moreover, we obtained mutants conferring the waxy phenotype for the first time in buckwheat. These findings demonstrate the utility of our F. esculentum assembly as a reference genome and promise to accelerate buckwheat research and breeding., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Diplonemid flagellates are among the most abundant and species-rich of known marine microeukaryotes, colonizing all habitats, depths, and geographic regions of the world ocean. However, little is known about their genomes, biology, and ecological role., Results: We present the first nuclear genome sequence from a diplonemid, the type species Diplonema papillatum. The ~ 280-Mb genome assembly contains about 32,000 protein-coding genes, likely co-transcribed in groups of up to 100. Gene clusters are separated by long repetitive regions that include numerous transposable elements, which also reside within introns. Analysis of gene-family evolution reveals that the last common diplonemid ancestor underwent considerable metabolic expansion. D. papillatum-specific gains of carbohydrate-degradation capability were apparently acquired via horizontal gene transfer. The predicted breakdown of polysaccharides including pectin and xylan is at odds with reports of peptides being the predominant carbon source of this organism. Secretome analysis together with feeding experiments suggest that D. papillatum is predatory, able to degrade cell walls of live microeukaryotes, macroalgae, and water plants, not only for protoplast feeding but also for metabolizing cell-wall carbohydrates as an energy source. The analysis of environmental barcode samples shows that D. papillatum is confined to temperate coastal waters, presumably acting in bioremediation of eutrophication., Conclusions: Nuclear genome information will allow systematic functional and cell-biology studies in D. papillatum. It will also serve as a reference for the highly diverse diplonemids and provide a point of comparison for studying gene complement evolution in the sister group of Kinetoplastida, including human-pathogenic taxa., (© 2023. The Author(s).)

Background: Supragastric belching (SGB) is a phenomenon where air is rapidly sucked from the pharynx into the esophagus and immediately expelled through abdominal straining. It is considered a behavior disorder and is increasingly recognized not only in patients with excessive belching, but also in those with reflux-like symptoms. Increased prevalence of esophageal hypomotility and increased acid exposure were previously reported in small cohorts of SGB patients. We aimed to clarify the impact of SGB on motility, reflux, and acid exposure in a large cohort of SGB patients., Methods: In a single-center database study, we searched for patients with pathological SGB. MII-pH and Manometry tracings were manually re-evaluated in all patients. Demographic, clinical, motility, reflux, and SGB-related data were gathered., Key Results: Three hundred and forty-eight patients were included. Heartburn, belching, and regurgitation were the most common symptoms. Ineffective esophageal motility (IEM) was found in 27% of patients. SGB related to 47% of all reflux and to 53.6% of acid reflux events, and accounted for 27.3% of acid exposure time (AET). In those with severe SGB, 62% of acid reflux events and 46% of AET were SGB-related., Conclusions & Inferences: Supragastric belching is common, associated with higher incidence of IEM and is responsible for almost a third of esophageal acid burden. The impact of SGB is proportional to its severity. Diagnosis of SGB should be sought in patients with excessive belching and in patients with refractory reflux symptoms. Recognizing SGB and treating patients with behavioral therapy may alleviate acid exposure and improve quality of life., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Two autophagy-related (ATG) ubiquitin-like conjugation systems, the ATG12 and ATG8 systems, play important roles in macroautophagy. While multiple duplications and losses of the ATG conjugation system proteins are found in different lineages, the extent to which the underlying systems diversified across eukaryotes is not fully understood. Here, in order to understand the evolution of the ATG conjugation systems, we constructed a transcriptome database consisting of 94 eukaryotic species covering major eukaryotic clades and systematically identified ATG conjugation system components. Both ATG10 and the C-terminal glycine of ATG12 are essential for the canonical ubiquitin-like conjugation of ATG12 and ATG5. However, loss of ATG10 or the C-terminal glycine of ATG12 occurred at least 16 times in a wide range of lineages, suggesting that possible covalent-to-non-covalent transition is not limited to the species that we previously reported such as Alveolata and some yeast species. Some species have only the ATG8 system (with conjugation enzymes) or only ATG8 (without conjugation enzymes). More than 10 species have ATG8 homologs without the conserved C-terminal glycine, and Tetrahymena has an ATG8 homolog with a predicted transmembrane domain, which may be able to anchor to the membrane independent of the ATG conjugation systems. We discuss the possibility that the ancestor of the ATG12 and ATG8 systems is more similar to ATG8. Overall, our study offers a whole picture of the evolution and diversity of the ATG conjugation systems among eukaryotes, and provides evidence that functional diversifications of the systems are more common than previously thought. Abbreviations : APEAR: ATG8-PE association region; ATG: autophagy-related; LIR: LC3-interacting region; NEDD8: neural precursor cell expressed, developmentally down-regulated gene 8; PE: phosphatidylethanolamine; SAMP: small archaeal modifier protein; SAR: Stramenopiles, Alveolata, and Rhizaria; SMC: structural maintenance of chromosomes; SUMO: small ubiquitin like modifier; TACK: Thaumarchaeota, Aigarchaeota, Crenarchaeota, and Korarchaeota; UBA: ubiquitin like modifier activating enzyme; UFM: ubiquitin fold modifier; URM: ubiquitin related modifier.

Dinoflagellates possess plastids that are diverse in both pigmentation and evolutionary background. One of the plastid types found in dinoflagellates is pigmented with chlorophylls a and b (Chl a + b ) and originated from the endosymbionts belonging to a small group of green algae, Pedinophyceae. The Chl a + b -containing plastids have been found in three distantly related dinoflagellates Lepidodinium spp., strain MGD, and strain TGD, and were proposed to be derived from separate partnerships between a dinoflagellate (host) and a pedinophycean green alga (endosymbiont). Prior to this study, a plastid genome sequence was only available for L. chlorophorum , which was reported to bear the features that were not found in that of the pedinophycean green alga Pedinomonas minor , a putative close relative of the endosymbiont that gave rise to the current Chl a + b -containing plastid. In this study, we sequenced the plastid genomes of strains MGD and TGD to compare with those of L. chlorophorum as well as pedinophycean green algae. The mapping of the RNA-seq reads on the corresponding plastid genome identified RNA editing on plastid gene transcripts in the three dinoflagellates. Further, the comparative plastid genomics revealed that the plastid genomes of the three dinoflagellates achieved several features, which are not found in or much less obvious than the pedinophycean plastid genomes determined to date, in parallel., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Matsuo, Morita, Nakayama, Yazaki, Sarai, Takahashi, Iwataki and Inagaki.)

By clarifying the phylogenetic positions of 'orphan' protists (unicellular micro-eukaryotes with no affinity to extant lineages), we may uncover the novel affiliation between two (or more) major lineages in eukaryotes. Microheliella maris was an orphan protist, which failed to be placed within the previously described lineages by pioneering phylogenetic analyses. In this study, we analysed a 319-gene alignment and demonstrated that M. maris represents a basal lineage of one of the major eukaryotic lineages, Cryptista. We here propose a new clade name 'Pancryptista' for Cryptista plus M. maris . The 319-gene analyses also indicated that M. maris is a key taxon to recover the monophyly of Archaeplastida and the sister relationship between Archaeplastida and Pancryptista, which is collectively called 'CAM clade' here. Significantly, Cryptophyceae tend to be attracted to Rhodophyta depending on the taxon sampling (ex., in the absence of M. maris and Rhodelphidia) and the particular phylogenetic 'signal' most likely hindered the stable recovery of the monophyly of Archaeplastida in previous studies.